Zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) monotherapy in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Primary analysis of the phase 2 randomized ROSEWOOD trial.
Authors: Pier Luigi Zinzani, Jiří Mayer, Rebecca Auer, Fontanet Bijou, Ana C. de Oliveira, Christopher Flowers, Michele Merli, Krimo Bouabdallah, Peter S. Ganly, Roderick Johnson, Sam Yuen, Ed Kingsley, Gayane Tumyan, Sarit E. Assouline, Elena Ivanova, Pil Kim, Jane Huang, Richard Delarue, Judith Trotman
Journal: Journal of Clinical Oncology (2022)

7510 Background: FL is the most common type of indolent non-Hodgkin lymphoma. Approved treatment options are limited for pts with R/R FL. In a phase 1b trial ( Blood Adv. 2020;4(19):4802-4811), ZO was found to be tolerable and associated with early signal of efficacy. ROSEWOOD (BGB-3111-212) is a phase 2, randomized study designed to assess efficacy and safety of ZO vs O in pts with R/R FL. Methods: Pts with R/R FL who received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomized 2:1 to receive either ZO or O. O was given in both arms on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and then every 8 weeks up to 20 doses maximum. Z (160 mg twice daily) was given until progressive disease (PD) or unacceptable toxicity; Pts with confirmed PD in the O arm were allowed to crossover to ZO. Primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoint included ORR by investigator after crossover. Primary analysis cutoff was October 8, 2021. Results: A total of 217 pts were randomized to ZO (n = 145) or O (n = 72). Median study follow-up was 12.5 mo; median age was 64 yrs. Incidence of high FL International Prognostic Index score was 53% (ZO) and 51% (O). Pts received a median of 3 prior lines of therapy, with 28% (ZO) and 25% (O) of pts receiving &gt; 3 lines. Proportion of pts refractory to rituximab, refractory to the most recent line of therapy, or with PD within 24 mo of initiation of first-line immunochemotherapy was 54%, 32% and 28% with ZO and 50%, 40% and 32% with O, respectively. The study met its primary endpoint: ORR was 68.3% with ZO vs 45.8% with O ( p= 0.0017). CRR was 37.2% (ZO) vs 19.4% (O); 18-mo DOR rate was 70.9% (ZO) vs 54.6% (O); and median PFS was 27.4 mo (ZO) vs 11.2 mo (O; hazard ratio [HR], 0.51 [95% CI, 0.32-0.81], p= 0.0040). Median time to new anti-lymphoma therapy or crossover was not evaluable (NE; ZO) vs 12.1 mo (O; HR, 0.37 [95% CI, 0.23-0.60], p&lt; 0.0001). ORR for 29 pts who crossed over to ZO was 24.1%. Median OS was NE; 18-mo OS probability was 85.4% (ZO) vs 72.6% (O). Most common any grade AEs in the ZO arm were thrombocytopenia (34.3%), neutropenia (27.3%), diarrhea (16.1%), fatigue (14.0%), constipation (13.3%), cough (11.9%), pyrexia (11.2%), and dyspnea (10.5%). Grade ≥3 AEs with incidence &gt; 5% with ZO were neutropenia (22.4%) and thrombocytopenia (14.0%); incidence of atrial fibrillation was 0.7% and major bleeding was 1.4%. Incidence of treatment-emergent AEs leading to death was 5.6% (ZO) and 9.9% (O). Conclusions: ZO demonstrated superior efficacy to O in treatment of pts with R/R FL. ZO had a favorable benefit-risk profile and represents a potential combination therapy for pts with R/R FL. Clinical trial information: NCT03332017.